Single-molecule super-resolution microscopy reveals heteromeric complexes of MET and EGFR upon ligand activation

  • Receptor tyrosine kinases (RTKs) orchestrate cell motility and differentiation. Deregulated RTKs may promote cancer and are prime targets for specific inhibitors. Increasing evidence indicates that resistance to inhibitor treatment involves receptor cross-interactions circumventing inhibition of one RTK by activating alternative signaling pathways. Here, we used single-molecule super-resolution microscopy to simultaneously visualize single MET and epidermal growth factor receptor (EGFR) clusters in two cancer cell lines, HeLa and BT-20, in fixed and living cells. We found heteromeric receptor clusters of EGFR and MET in both cell types, promoted by ligand activation. Single-protein tracking experiments in living cells revealed that both MET and EGFR respond to their cognate as well as non-cognate ligands by slower diffusion. In summary, for the first time, we present static as well as dynamic evidence of the presence of heteromeric clusters of MET and EGFR on the cell membrane that correlates with the relative surface expression levels of the two receptors
Author:Marie-Lena I. E. Harwardt, Mark S. Schröder, Yunqing Li, Sebastian MalkuschORCiDGND, Petra Freund, Shashi Gupta, Nebojsa Janjic, Sebastian Strauss, Ralf JungmannORCiDGND, Marina DietzORCiDGND, Mike HeilemannORCiDGND
Parent Title (English):International journal of molecular sciences
Place of publication:Basel
Document Type:Article
Date of Publication (online):2020/04/17
Date of first Publication:2020/04/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/08/11
Tag:DNA-PAINT; EGFR; MET; receptor cross-interaction; receptor tyrosine kinases; single-molecule localization microscopy; single-particle tracking
Issue:8, art. 2803
Page Number:20
First Page:1
Last Page:20
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Open-Access-Publikationsfonds:Biochemie, Chemie und Pharmazie
Licence (German):License LogoCreative Commons - Namensnennung 4.0